Article excerpt

Introduction

The withdrawal of the first rotavirus vaccine to be licensed in the United States (RotaShield, Wyeth-Lederle Vaccines, Philadelphia, PA, United States), due to an unexpected association with intussusception, resulted in a major setback in the effort to reduce the global burden of rotavirus gastroenteritis. (1-3) Although the risk of intussusception following immunization with RotaShield is low, it has posed a major challenge to the future development of a safe and effective vaccine. (2) Large-scale clinical trials are now required to detect a risk of intussusception of< 1 in 10 000. (4-6) Baseline intussusception surveillance is needed in sites where trials of rotavirus vaccines are planned, and post-licensure intussusception surveillance may also be required by some licensing agencies.

Intussusception is the invagination of the bowel by a more proximal segment. The intussusception can be propelled distally by peristalsis, resulting in intestinal obstruction and vascular compromise of the intestine. Prompt identification and reduction by air enema or hydrostatic enema or by surgery is vital to minimize the morbidity and mortality that may be associated with this condition. To assist in the early recognition of infants with intussusception a clinical case definition for the diagnosis of acute intussusception in infants and young children was developed by WHO and the Brighton Collaboration. (7) The aim of the clinical case definition is to provide practical clinical criteria that will identify the majority of children with intussusception presenting at a variety of health-care settings. The clinical case definition that was developed showed promise (sensitivity = 97%; specificity = 87-91%) in a retrospective study in a tertiary care hospital in Australia. (8) The aim of this study was to validate the clinical case definition for intussusception by assessing the performance of the criteria prospectively in parallel studies in a developed country and in a developing country where there is a high incidence of intussusception. Each component of the definition was analysed to assess the reliability of individual symptoms and signs as well as groups of symptoms and signs to assess the sensitivity and specificity of the definition.

Methods

Prospective studies were performed at the National Hospital of Pediatrics in Hanoi, Viet Nam, during a 14-month period (1 November 2002-31 December 2003) and the Royal Children's Hospital in Melbourne, Australia, over a 24-month period (19 March 2002-18 March 2004). The study was approved by the Ethics Committee of the Ministry of Health, Viet Nam, and the Ethics in Human Research Committee of the Royal Children's Hospital, Melbourne. Free and informed consent was obtained from each child's legal guardian.

The sensitivity of the clinical case definition was evaluated in infants aged < 2 years presenting to the hospitals. Medical staff completed a standardized questionnaire (in English or Vietnamese) that reviewed the symptoms and signs described in the clinical case definition. A diagnostic procedure was then performed to confirm or exclude intussusception. Only patients with the diagnosis of primary idiopathic intussusception confirmed by air enema or surgery were included in the calculation of sensitivity. Validation of cases of intussusception diagnosed by air enema was conducted by an independent radiologist (MdC) blinded to the infant's status who reviewed radiographs of the air enema examination from before and after air reduction. Surgical notes for all patients diagnosed with intussusception at surgery were reviewed by an independent observer to confirm the diagnosis.

The specificity of the definition was assessed in patients with symptoms and signs that may occur in intussusception but for whom an alternative diagnosis was established (non-intussusception control group).

The non-intussusception control group included infants aged < 2 years presenting to the hospitals with one or more of the following symptoms or signs: vomiting without respiratory symptoms, abdominal pain, rectal bleeding, bowel obstruction or abdominal mass. …